The objectives of this study are (1) the characterization of some microsomal, mitochondrial or soluble conjugating and hydrating enzymes of extrahepatic tissues as compared to the liver enzymes, (2) to determine the effects of selected xenobiotics upon these enzymes, (3) to assess the relative importance in vivo of this extrahepatic enzyme activity as compared to the liver, following ingestion or administration of chemicals and drugs (substrates) via various routes including inhalation, (4) to investigate the perinatal development of some detoxifying enzymes in hepatic and extrahepatic tissues of a few species and to determine the protective role, if any, of these enzymes against localized tissue toxicity induced by chemically reactive electrophilic metabolites, such as epoxides, (5) to compare the metabolism of chemically reactive epoxides and their unsaturated hydrocarbon precursors in an isolated perfused rabbit lung preparation, and (6) to assess the role of the cell's nucleus (nuclear membrane and nucleoplasm) in the formation and subsequent biotransformation of chemically reactive metabolites.